Integrated Analysis of Slow Transit Constipation and Colorectal Cancer Reveals the Co-Pathogenic Targets and Their Potential Clinical Value.

IF 1.9 4区医学 Q3 ONCOLOGY

Cancer Investigation Pub Date : 2025-05-01 Epub Date: 2025-06-02 DOI:10.1080/07357907.2025.2506102

Yan Wang, Jiawei Sun, Di Wang, Hongguang Liu, Qing Ma, Shuo Chen

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引用次数: 0

Abstract

Background: Slow transit constipation (STC) is a potential risk of the onset of colorectal cancer (CRC). Thus, the purpose of this work is to focus on the co-pathogenic targets between STC and CRC, meanwhile evaluating their prognostic value for CRC.

Methods: The miRNA and mRNA data of STC and CRC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The prognostic signature was constructed based on hub genes, which identified using differential expression analysis and LASSO Cox regression analysis. The hub genes were validated employing multiple public databases. Enrichment analysis was employed to elucidate their functions. Survival analysis was performed using Kaplan-Meier method. Transcription factor binding sites were predicted and verified using FIMO and ChIP-seq database, respectively.

Results: We identified four common key differentially expressed miRNAs of STC and CRC, including hsa-miR-340, hsa-miR-30b, hsa-miR-20b, and hsa-miR-29c (p-value <0.05), and their targets were involved in the CRC's metabolic processes (all p-values <0.05). We developed a prognostic signature based on nine hub genes, and patient prognosis could be predicted employing Risk score = 0.099063054* NOG + 0.074815408* PLD5 + 0.003499667* NOVA1 + 0.051762032*DTNA + 0.050495722* GPR26 + 0.045057094* TNFAIP8L3 + 0.097209257* SLC29A4+ (-0.246941474)* CCNJL + 0.039294168* TRABD2B. High-risk patients exhibited significantly poorer prognosis (p-value <0.05). The hub genes CCNJL, NOVA1, PLD5, and SLC29A4 were significantly down-regulated targets of hsa-miR-340 in the CRC samples (p-value <0.05). Functional analyses suggested their involvement in immune-related processes (all p-values <0.05). Our exploration of upstream regulators revealed six and one reliable transcription factors for CCNJL and SLC29A4, respectively.

Conclusion: This study delved into common biomarkers between STC and CRC, and developed a reliable prognostic signature for CRC.

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慢传输型便秘与结直肠癌的综合分析揭示其共同致病靶点及其潜在临床价值。

背景：慢传输型便秘（STC）是结直肠癌（CRC）发病的潜在风险之一。因此，本工作的目的是关注STC与CRC之间的共同致病靶点，同时评估其对CRC的预后价值。方法：从Cancer Genome Atlas和Gene Expression Omnibus数据库中下载STC和CRC的miRNA和mRNA数据。通过差异表达分析和LASSO Cox回归分析确定枢纽基因的预后特征。利用多个公共数据库对中心基因进行验证。富集分析证实了它们的功能。采用Kaplan-Meier法进行生存分析。分别使用FIMO和ChIP-seq数据库预测和验证转录因子结合位点。结果：我们鉴定出4种常见的STC和CRC关键差异表达mirna，包括hsa-miR-340、hsa-miR-30b、hsa-miR-20b和hsa-miR-29c （p值NOG + 0.074815408* PLD5 + 0.003499667* NOVA1 + 0.051762032*DTNA + 0.050495722* GPR26 + 0.045057094* TNFAIP8L3 + 0.097209257* SLC29A4+ (-0.246941474)* CCNJL + 0.039294168* TRABD2B）。高危患者预后明显较差(p值CCNJL、NOVA1、PLD5和SLC29A4在CRC样本中分别是hsa-miR-340的显著下调靶点（p值CCNJL和SLC29A4）。结论：本研究深入探讨了STC和CRC之间的共同生物标志物，并建立了可靠的CRC预后标志。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Investigation 医学-肿瘤学

CiteScore

3.80

自引率

4.20%

发文量

审稿时长

8.5 months

期刊介绍： Cancer Investigation is one of the most highly regarded and recognized journals in the field of basic and clinical oncology. It is designed to give physicians a comprehensive resource on the current state of progress in the cancer field as well as a broad background of reliable information necessary for effective decision making. In addition to presenting original papers of fundamental significance, it also publishes reviews, essays, specialized presentations of controversies, considerations of new technologies and their applications to specific laboratory problems, discussions of public issues, miniseries on major topics, new and experimental drugs and therapies, and an innovative letters to the editor section. One of the unique features of the journal is its departmentalized editorial sections reporting on more than 30 subject categories covering the broad spectrum of specialized areas that together comprise the field of oncology. Edited by leading physicians and research scientists, these sections make Cancer Investigation the prime resource for clinicians seeking to make sense of the sometimes-overwhelming amount of information available throughout the field. In addition to its peer-reviewed clinical research, the journal also features translational studies that bridge the gap between the laboratory and the clinic.